Analysis of Immunoglobulin A and M gene expression and plasma cells in bronchial tissue from COPD patients with high blood eosinophil counts

Author(s):  
Thomas Southworth ◽  
Umme Kolsum ◽  
Andrew Higham ◽  
Sriram Sridhar ◽  
Tuyet-Hang Pham ◽  
...  
2019 ◽  
Vol 20 (16) ◽  
pp. 1670-1679 ◽  
Author(s):  
Olorunfemi A. Oshagbemi ◽  
Jephthah O. Odiba ◽  
Abraham Daniel ◽  
Ismaeel Yunusa

Introduction: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2019 recommends the use of absolute blood eosinophil count as a guide for the escalation and de-escalation of inhaled corticosteroids (ICS) in the pharmacological management of patients with chronic obstructive pulmonary disease (COPD). We evaluated the risk of moderate or severe exacerbations among patients escalating and de-escalating ICS therapy by absolute blood eosinophil thresholds in this systematic review. Methods: Through a comprehensive literature search of Pubmed/MEDLINE, EMBASE, and clinical trial sites up to April 2019, we identified relevant studies. We used generic inverse variance method with fixed-effects estimates to compare the risk of moderate or severe exacerbations among COPD patients with elevated blood eosinophil counts exposed to inhaled corticosteroids (ICS) versus non-ICS treatments groups expressed as risk ratios. Results: Ten studies (8 randomised control trials and 2 observational studies) were included, with a total of 85,059 COPD patients. In our pooled analysis, we found an overall reduction in risk of moderate or severe exacerbations in patients with absolute blood eosinophil thresholds ranging from ≥ 100 to ≥ 340 cells/µL among patients escalating ICS (RR, 0.77, 95% CI, 0.73-0.81). For studies evaluating the effects of de-escalation of ICS on moderate to severe exacerbations using blood eosinophil thresholds of ≥ 300 to ≥ 340 cells/µL had an increased risk of moderate or severe exacerbations following the de-escalation of ICS (RR, 1.66, 95% CI, 1.31-2.10). Conclusion: This study confirms the validity of the recommended absolute blood eosinophil count thresholds for the escalation and de-escalation of ICS among COPD patients. However, this recommendation is for COPD patients with prior exacerbations rather than among newly diagnosed COPD patients as observed in this study. COPD patients with current or past history of asthma represent a unique phenotypic group which should be further evaluated.


2019 ◽  
Vol 9 ◽  
Author(s):  
Carmen Calero ◽  
Jose Luis López-Campos ◽  
Lourdes Gómez Izquierdo ◽  
Rocio Sánchez-Silva ◽  
Jose Luis López-Villalobos ◽  
...  

Background: Aquaporins AQP1 and AQP5 are highly expressed in the lung. Recent studies have shown that the expression of these proteins may be mechanistically involved in the airway inflammation and in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the expression of AQP1 and AQP5 in the bronchial tissue and the lung parenchyma of patients with COPD and COPD-resistant smokers. Methods: Using a case–control design, we selected a group of 15 subjects with COPD and 15 resistant smokers (smokers without COPD) as a control, all of whom were undergoing lung resection surgery due to a lung neoplasm. We studied the expression of AQP1 and AQP5 in the bronchial tissue and the lung parenchyma by means of immunohistochemistry and reverse-transcription real-time polymerase chain reaction. Tissue expression of AQP1 and AQP5 was semi-quantitatively assessed in terms of intensity and expression by immunohistochemistry using a 4-point scale ranging from 0 (none) to 3 (maximum). Results: There were no significant differences in gene expression between COPD patients and resistant smokers both in the bronchial tissue and in the lung parenchyma. However, AQP1 gene expression was 2.41-fold higher in the parenchyma of smokers with COPD compared to controls, whereas the AQP5 gene showed the opposite pattern, with a 7.75-fold higher expression in the bronchus of smokers with COPD compared with controls. AQP1 and AQP5 proteins were preferentially expressed in endothelial cells, showing a higher intensity for AQP1 (66.7% of cases with an intensity of 3, and 93.3% of subjects with an extension of 3 among patients with COPD). Subtle interstitial disease was associated with type II pneumocyte hyperplasia and an increased expression of AQP1. Conclusions: This study provides pilot observations on the differences in AQP1 and AQP5 expression between COPD patients and COPD-resistant smokers. Our findings suggest a potential role for AQP1 in the pathogenesis of COPD.


2021 ◽  
Author(s):  
Ahmed Yousuf ◽  
Hamish McAuley ◽  
Omer Elneima ◽  
Christopher E Brightling

Abstract Background Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity and mortality. To improve the health status and reduce symptom burden, it is important to identify a group of patients with similar characteristics and prognosis, called clinical phenotypes. Herein we shall review the different phenotypes of COPD. Sources of data Keywords (COPD, phenotype, acute exacerbation) search was conducted in PubMed, Google Scholar. Areas of agreement Those with raised blood eosinophil counts respond better to steroid therapy at stable state and exacerbation. Areas of controversy There is no universally accepted blood eosinophil cut-off value that will indicate favourable response to corticosteroids and potentially for future biologic therapy. Growing points There is an urgent need for further therapeutic options for COPD patients with non-eosinophilic inflammation. Areas timely for developing research Well-designed COPD trials with identification of phenotypes for more personalization of the treatment of COPD.


2019 ◽  
Vol 53 (5) ◽  
pp. 1900164 ◽  
Author(s):  
Dave Singh ◽  
Alvar Agusti ◽  
Antonio Anzueto ◽  
Peter J. Barnes ◽  
Jean Bourbeau ◽  
...  

Precision medicine is a patient-specific approach that integrates all relevant clinical, genetic and biological information in order to optimise the therapeutic benefit relative to the possibility of side-effects for each individual. Recent clinical trials have shown that higher blood eosinophil counts are associated with a greater efficacy of inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD) patients. Blood eosinophil counts are a biomarker with potential to be used in clinical practice, to help target ICS treatment with more precision in COPD patients with a history of exacerbations despite appropriate bronchodilator treatment.The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 pharmacological treatment algorithms, based on the ABCD assessment, can be applied relatively easily to treatment-naive individuals at initial presentation. However, their use is more problematic during follow-up in patients who are already on maintenance treatment. There is a need for a different system to guide COPD pharmacological management during follow-up.Recent large randomised controlled trials have provided important new information concerning the therapeutic effects of ICSs and long-acting bronchodilators on exacerbations. The new evidence regarding blood eosinophils and inhaled treatments, and the need to distinguish between initial and follow-up pharmacological management, led to changes in the GOLD pharmacological treatment recommendations. This article explains the evidence and rationale for the GOLD 2019 pharmacological treatment recommendations.


2019 ◽  
Vol 54 (4) ◽  
pp. 1900633 ◽  
Author(s):  
Umme Kolsum ◽  
Thomas Southworth ◽  
Natalie Jackson ◽  
Dave Singh

1996 ◽  
Vol 5 (2) ◽  
pp. 113-115 ◽  
Author(s):  
G. Di Lorenzo ◽  
P. Mansueto ◽  
M. Melluso ◽  
G. Candore ◽  
D. Cigna ◽  
...  

We have analysed the relationship of blood eosinophil count and serum eosinophil cationic protein (ECP) levels in patients with acute and chronic idiopathic urticaria. The ECP levels and eosinophil counts were measured in the peripheral blood of 15 patients with acute urticaria, 25 with chronic idiopathic urticaria and 10 normal healthy subjects. Blood eosinophil counts and serum ECP levels increased in all patients with acute urticaria. Concerning patients affected by chronic urticaria, taking into account the recrudescence of the disease at the moment of taking the blood sample, only symptomatic patients showed increased eosinophil blood values whereas serum ECP levels were increased both in symptomatic and asymptomatic patients. Furthermore, serum ECP levels in chronic urticaria did not correlate with the peripheral eosinophil counts, as they did in acute urticaria. The results of the present study indicate that eosinophils may play a role in the inflammatory mechanisms in patients with acute and chronic urticaria showing a positive correlation between serum ECP levels and disease activity.


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